Pio marfori



UNITED STATES PATENT O FICE.

PIO MARFORI, OF FERRARA, ITALY, AND OSWALl) SCHNIEDEBERG, OF STRAS- BURG, ALSACE, ASSIGNORS TO 0. F. BOEHRINGER 8a SOEHNE, OF WALD- HOF, NEAR MANNHEIM, GERMANY.

lRON-ALBUMEN PREPARATION AND MODE OF MAKING SAME.

SPECIFICATION forming part of Letters ,Patent No. 505,986, dated October 3, 1893 Application filed April 13,1893. Serial No. 470,247. (Specimena) Kingdom of Italy, and OSWALD SCHNIEDE-Y BEEG, a citizen of the German Empire, and res1d1ng at Strasburg, Alsace, German Empire, have invented certain new and useful Improvements in Iron Derivatives of Albumen and the Method of Preparing the Same; and we 10 do hereby declare the following to be a full, clear,'and exact description of the invention, such as will enable others skilled in the art to which it appertains to make and use the same.

This invention relates to the artificial production of iron derivatives of albumen essentially differing in constitution from the heretofore known albuminates of iron or iron salts of albuminous acids.

The object of the said invention is to produce iron compounds of the same character and capable of ready assimilation in the same proportion as certain iron derivatives of albumen existing in food and in the animal organism. These compounds may be used,

first, as medicinal compounds which may be prescribed for the usual therapeutic purposes and administered in doses which are readily determined and which vary according to the amount of iron which it is desired to intro- 0 duce into the system; and secondly, as an article of food for children and other anaemic persons, in which capacity it may be used either alone or as an addition to food, e. g.,

milk.

Our invention for this purpose consists in the methods, steps and features and the article to be hereinafter described and pointed out in the claims.

When albuminous substances, such as eg 0 albumen, serum-albumen, fibrin, muscle-albumen, &c., are heated with alkalies there are produced so-called alkaline albuminates. Similar salts are produced with calcium and iron, &;o. The present invention, however, is

5 designed to produce iron-derivatives of albuminous acid which widely difier and are sharply distinguished from the iron salts of albuminous acid, by very radical characteristics and properties. The preferred method an albumen, such as egg-albumen, and dis-'- solve the same in two thousand parts of cold distilled water by shaking. This solution is treated successively with, first, twenty-five part of ferrous or ferric tartrate dissolved in two hundred and fifty parts of distilled water and neutralized with a ten per cent. soda-lye; second, one hundred parts of a ten per cent. neutral solution of tartrate of sodium; third, thirty eight parts of a ten per cent. soda lye. The resultant solution is warmed to 90 centigrade until a perfectly clear thin brownish red solution is attained, that is to say, until the deep or black-red color which occurs after about one to two hours, has changed to a somewhat lighter red. This generally occurs after from two and a half to four hours. In order to remove the great surplus of alkali,

'the solution, after cooling, is treated with a twenty-five per cent. solution of tartaric acid, until acid reaction occurs and the excess of acid is then removed by adding a twenty-five per cent. solution of ammonia and continuing such addition until adistinct alkaline re action takes place. The alkaline solution is then kept at a temperature of 90 centigrade, for not less than twelve, and, preferably for forty-eight hours, whereupon the same is allowed to cool and is then treated with a twentyfive per cent. solution of tartaric acid until the same reacts distinctly acid, whereby the iron derivative of albumen is precipitated as a voluminous precipitate in color and form similar to freshly precipitated ferric or ferrous hydrate and in this way separated from all other noxious and undesirable salts and constituents. The precipitate is then put in the filter and washed until no more iron can be detected in the filtrate.

To further purify the precipitate or moist mass obtained the same is dissolved in fourteen hundred parts of distilled water, to which twenty parts of a twenty-five per cent. am monla solution and twenty parts of a ten per cent. neutral, or rather weakly alkaline solution of tartrate of ammonium are added and then heated to centigrade, for not less than twelve and preferably forty-eight hours. The mixture is then thoroughly cooled and treated with a twenty-five per cent. solution of tartaric acid, until a distinct acid reaction takes place, when the precipitate formed is filtered and washed in the filter with distilled water, until the acid reaction disappears. The resultant moist mass is then dried at a slightly raised temperature, thus forming an amorphous dark or light-brown colored powder or thin scales of dark or light-brown color.

The above constitutes what we consider the best way of carrying our invention into effect. But the method thus detailed may be variously and widely modified without departing from ourinvention. Thus, for exam ple, in place of the soda salt of tartaric acid, other alkali salts of tartaric and other acids may be used, provided they are capable of keeping the iron in solution in the presence of alkaline solutions of lyes. And it is even possible to dispense with such alkali salts in cases where the albuminous substances are themselves capable of retaining the iron salts in solution in the presence of an alkali,such as soda-lye, the. It should be observed, more over, that other acids may be used in lieu of the tartaric acid, and other iron salts may be used in lieu of those above set forth.

Other alkaline solutions of lyes than those set forth may also be used with advantage. The temperature and proportions may also be modified within certain limits. The temperature especially may be considerably less than 90 centigrade, and the compound may be formed even at ordinary temperature, in which case, however, its formation is very considerably delayed, the rule being that time consumed in such formation increases as the temperature is diminished or lowered.

In general it should be distinctly understood, that the most essential feature of our process consists in keeping continuously for a long periodwhich should in no case be less than twelve hours--an albuminous substance in the presence of an iron salt, an alkali and, preferably, though not necessarily, an alkalisalt. The iron derivative of albumen so obtained is of a dark or light-brown color, insoluble in water andslightly acidified water, but soluble in a great surplus of tartaric acid. On the otherhand,the-same is readily soluble in weakly alkaline cold water directly after precipitation. When dried it is readily soluble in weakly alkaline warm water. It contains about from seven to ten per cent. iron, but not in the form of an iron salt. It is an amorphous powder and may be also prepared in thin scales. When heated over 50 centigrade, it decomposes. In a neutral solution it does not coagulate by boiling.

The iron derivatives of albumen formed at the beginning of the reactions in our process is subsequently so transposed by the long continued heating to 90 Centigrade in the presence of an alkali, such as soda-lye (and, preferably, an alkali-salt such as the tartrate of soda), that the molecule of the albumen 1s changed and the iron forms a part of such molecule and is there bound so intimately that it cannot be separated by the ordinary reagents.

Only by a complete decomposition of the compound can the iron be brought in a form in which it can be detected. It is due to this fact that the iron of this preparation, which is capable of certain and ready assimilation when introduced into the animal and human system, cannot be withdrawn by the snlphureted hydrogen present in the intestines and cannot be modified to such an extent, as is the case with other preparations of iron, whose iron is at once precipitated as sulfid of iron by the hydrogen sulfid. On the other hand, the iron in the present compound as a derivative of albumen is not so intimately bound in the molecule as in the ferroand ferri-cyanides which are without value as therapeutic and nutrative iron-compounds, and hence, are never used for such purposes.

In order to define the present compound with still greater accuracy, the following reaction or test, which serves to sharply identify the same, is given: Twenty cubic centimeters of an ammoniacal solution containing 0.06 grams of the iron derivative of albumen formed by our process are not modified within five minutes after a drop of a fifty per cent. aqueous solution of sulphid of ammonium (Fresenins: Qualitative Analsye fourteenth edition, page 68) has been added, and after twenty-five minutes the same does not attain an opaque black color, after such addition.

As already stated the importance of this invention is mainly due to the fact that the product is essentially similar to iron compounds formed by the animal organism itself, and capable of being readily assimilated in the mentioned proportion therein, and that it may hence be easily and conveniently administered in such doses as will result in a sufficient supply to and reception in the system of the required iron. These facts have been demonstrated by extensive and exhastive experiments. Not less important is its use as a food-compound which may be used alone, inasmuch as it essentially consists solely of albumen and iron, or as an addition to articles of food, as, for example,milk. The milk which is given to infants and other anemic persons is considerably increased in value and improved in its nutritive properties by this addition, and in this form may serve as the principal and even exclusive article of diet. WVe consider this last property which has been demonstrated beyond a peradventure as one of the greatest advantages resulting from our invention.

Our new food compound or medicine may be used in the dried solid state or in solution.

What we claim, and desire to secure by Letters Patent, is

1. The process of obtaining an iron compound capable of resorption in the animal organism, which consists in keeping an albuminous substance in solution in the presence of an iron salt and an alkali, substantially as set forth.

2. The process of obtaining an iron compound capable of resorption in the mentioned proportion in theanimal organism, which consists in heating albuminous substances in the presence of an iron salt and an'alkali, substantially as set forth.

3. The process of obtaining an iron compound capable of resorption in the animal organism, which consists in adding albuminous substances to an iron salt in the presence of an alkali and heating the mixture for a period of not less than twelve hours, substantially as set forth.

4. The process of obtaining an iron compound capable of resorption in the mentioned proportion in the animal organism, which consists in heating an albuminous substance in solution in the presence of an iron salt and an alkali for a period of about two and a half to four hours, then treating the same with an acid to remove the alkali, then again rendering the same alkaline and finally heating for a period not less than twelve hours, substantially as set forth.

5. The process of obtaining an iron compound capable of resorption in the mentioned proportion in the animal organism, which consists in adding to a solution of albumen,

a solution of an iron salt, a neutral solution of an alkali-salt and an alkaline solution, then heating for a period of'abont two and a half to'four hours, then removing the surplus of alkali by an'acid, then again rendering the solution alkaline and finally heating the alkaline solution for a long period of not less than twelve hours, substantially as set forth. 7

6. The process of obtaining an iron compound capable of resorption in the mentioned proportion in the animal organism, which consists in adding successively to a solution of an albumen, a solution of an iron salt, a neutral solution of tartrate of sodium, and soda-lye, then warming the resultant liquid for about two and one half to four hours, then adding an acid solution to remove the surplus of alkali, then again rendering the solution alkaline and then keeping the solution at a temperature of about 90 centigrade, for

proportion in theanimal organism, which consists in keeping albuminous substances in solution in the presence of an iron salt and an alkali, and then precipitating the result- 9 ing iron derivative of albumen by an acid solution for removing noxious and undesirable salts and other constituents, substantially as set forth. I

8. The process of obtaining an iron compound capable of resorption in the mentioned proportion in the animal organism, which consists in heating albuminous substances in the presence of an iron salt and an alkali, and then precipitating the resulting iron derivative of albumen by a solution of tartaric acid, substantially as set forth.

9. The process of obtaining an iron compound capable of resorption in the mentioned proportion in the animal organism, which consists in adding successively to a solution of an albumen, a solution of tartrate of iron, a neutral solution of tartrate of sodium and a soda-lye, then warming the resultant solution to centigrade, for from two and a half to four hours, then adding a solution of tartaric acid to remove the surplus of alkali and then adding ammonia solution to render the liquid alkaline and finally keeping the mixture at a temperature of 90, centigrade, for a period of not less than twelve hours, substantially as set forth.

10. The process of obtaining an iron compound capable of resorption in the mentioned proportion in the animal organism, which consists in heating albuminous substances in solution in the presence of an iron salt and alkali, and then precipitating the resulting iron derivative of albumen by an acid solution, then purifying the precipitate by filtering and dissolving in distilled water mixed with a solution of ammonia and a solution of tartrate of ammonia and then keeping the solution at 90, centigrade, for a long period of time, then cooling and precipitating the iron derivative of albumen by tartaric acid to remove noxious salts, substantially as set forth.

11. The process of obtaining an iron compound capable of resorption in the mentioned proportion in the animal organism, which consists in adding successively to a solution of an albumen, a solution of tartrate of iron, a neutral solution of tartrate of sodium and a soda-lye, then warming the resultant solution to 90, centigrade, for from two and a half to fourhou'rs, then adding a solution of tartaric acid to remove the surplus of alkali and then adding ammonia solution to render the liquid alkaline and finally keeping the mixture at a temperature of 90, centigrade, for a period of not less than twelve hours, then allowing the same to cool, and then treating it with a solution of tartaric of ammonia, reacts in the manner hereinbefore specified.

In testimony whereof we affix our signatures in presence of two witnesses.

PIO MARFORI. OSWALD SCHNIEDEBERG.

Witnesses as to P10 Martori: ERNESTO MICQINETI, SPIRITO BERNARDO.

Witnesses as to O. Schniedeberg:

ERNEST THEoooR, CARL J ACOBY. 

